Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 6/2011

01.12.2011

Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina

verfasst von: E. Amosova, E. Andrejev, I. Zaderey, U. Rudenko, C. Ceconi, R. Ferrari

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 6/2011

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The antianginal and anti-ischemic efficacy of the selective I f inhibitor ivabradine is established in patients with stable angina in monotherapy and in combination with other antianginals, including beta-blocker. This pilot study compared the antianginal and anti-ischemic efficacy and hemodynamic profile of ivabradine plus 5 mg bisoprolol versus those of 10 mg bisoprolol in patients with stable angina.

Patients and methods

Twenty-nine patients with stable angina and moderate left ventricular systolic dysfunction already on bisoprolol 5 mg od were randomized into 2 groups. Group 1 (n = 17) received ivabradine (5–7.5 mg bid) in addition to bisoprolol 5 mg od, while in group 2 (n = 12) bisoprolol was uptitrated first to 7.5 mg and then 10 mg od. Patients underwent a treadmill test, 6-minute walking test, and echocardiography at baseline and after 2 months.

Results

Mean resting heart rate decreased in both groups, from 76.6 ± 4.6 bpm to 59.3 ± 2.5 bpm (P < 0.001) in group 1 and from 75.9 ± 3.0 bpm to 60.5 ± 2.3 bpm (P = 0.002) in group 2. The effect on resting heart rate did not differ significantly between the two groups. However, more patients became asymptomatic in group 1 than in group 2. Addition of ivabradine also improved exercise capacity, as shown by the results of the 6-minute walking and exercise tolerance tests, whereas in group 2 neither parameter was significantly affected. Chronotropic reserve significantly improved with ivabradine, but not with bisoprolol 10 mg.

Conclusions

These results suggest that combining ivabradine with low dose bisoprolol in stable angina patients produces additional antianginal and anti-ischemic benefits and improves chronotropic reserve.
Literatur
1.
Zurück zum Zitat Fox K, Borer JS, Camm AJ, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50:823–30.PubMedCrossRef Fox K, Borer JS, Camm AJ, et al. Resting heart rate in cardiovascular disease. J Am Coll Cardiol. 2007;50:823–30.PubMedCrossRef
2.
Zurück zum Zitat DiFrancesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res. 2006;53:399–406.PubMedCrossRef DiFrancesco D. Funny channels in the control of cardiac rhythm and mode of action of selective blockers. Pharmacol Res. 2006;53:399–406.PubMedCrossRef
3.
Zurück zum Zitat Borer JS, Fox K, Jaillon P, Lerebours G. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107:817–23.PubMedCrossRef Borer JS, Fox K, Jaillon P, Lerebours G. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial. Circulation. 2003;107:817–23.PubMedCrossRef
4.
Zurück zum Zitat Ruzyllo W, Tendera M, Ford I, Fox KM. Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial. Drugs. 2007;67:393–405.PubMedCrossRef Ruzyllo W, Tendera M, Ford I, Fox KM. Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial. Drugs. 2007;67:393–405.PubMedCrossRef
5.
Zurück zum Zitat Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26:2529–36.PubMedCrossRef Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26:2529–36.PubMedCrossRef
6.
Zurück zum Zitat Tardif JC, Ponikowski P, Kahan T. Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4 month, randomized, placebo-controlled trial. Eur Heart J. 2009;30:540–8.PubMedCrossRef Tardif JC, Ponikowski P, Kahan T. Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4 month, randomized, placebo-controlled trial. Eur Heart J. 2009;30:540–8.PubMedCrossRef
7.
Zurück zum Zitat Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.PubMedCrossRef Fox K, Ford I, Steg PG, Tendera M, Ferrari R. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.PubMedCrossRef
8.
Zurück zum Zitat Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled trial. Lancet. 2010;376:875–85.PubMedCrossRef Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled trial. Lancet. 2010;376:875–85.PubMedCrossRef
9.
Zurück zum Zitat Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J. 2009;30:2337–45.PubMedCrossRef Fox K, Ford I, Steg PG, Tendera M, Robertson M, Ferrari R. Relationship between ivabradine treatment and cardiovascular outcomes in patients with stable coronary artery disease and left ventricular systolic dysfunction with limiting angina: a subgroup analysis of the randomized, controlled BEAUTIFUL trial. Eur Heart J. 2009;30:2337–45.PubMedCrossRef
10.
Zurück zum Zitat Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2:358–67.PubMed Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr. 1989;2:358–67.PubMed
11.
Zurück zum Zitat Elhendy A, Mahoney DW, Khandheria BK, Burger K, Pellikka PA. Prognostic significance of impairment of heart rate response to exercise: impact of left ventricular function and myocardial ischemia. J Am Coll Cardiol. 2003;42:823–30.PubMedCrossRef Elhendy A, Mahoney DW, Khandheria BK, Burger K, Pellikka PA. Prognostic significance of impairment of heart rate response to exercise: impact of left ventricular function and myocardial ischemia. J Am Coll Cardiol. 2003;42:823–30.PubMedCrossRef
12.
Zurück zum Zitat Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006;27:1341–81.PubMedCrossRef Fox K, Garcia MA, Ardissino D, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J. 2006;27:1341–81.PubMedCrossRef
13.
Zurück zum Zitat Witte KK, Cleland JG, Clark AL. Chronic heart failure, chronotropic incompetence, and the effects of beta blockade. Heart. 2006;92:481–6.PubMedCrossRef Witte KK, Cleland JG, Clark AL. Chronic heart failure, chronotropic incompetence, and the effects of beta blockade. Heart. 2006;92:481–6.PubMedCrossRef
14.
Zurück zum Zitat Villella M, Villella A, Barlera S, Franzosi MG, Maggioni AP. Prognostic significance of double product and inadequate double product response to maximal symptom-limited exercise stress testing after myocardial infarction in 6296 patients treated with thrombolytic agents. GISSI-2 Investigators. Grupo Italiano per lo Studio della Sopravvivenza nell-Infarto Miocardico. Am Heart J. 1999;137:443–52.PubMedCrossRef Villella M, Villella A, Barlera S, Franzosi MG, Maggioni AP. Prognostic significance of double product and inadequate double product response to maximal symptom-limited exercise stress testing after myocardial infarction in 6296 patients treated with thrombolytic agents. GISSI-2 Investigators. Grupo Italiano per lo Studio della Sopravvivenza nell-Infarto Miocardico. Am Heart J. 1999;137:443–52.PubMedCrossRef
15.
Zurück zum Zitat Simon L, Ghaleh B, Puybasset L, Giudicelli JF, Berdeaux A. Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther. 1995;275:659–66.PubMed Simon L, Ghaleh B, Puybasset L, Giudicelli JF, Berdeaux A. Coronary and hemodynamic effects of S 16257, a new bradycardic agent, in resting and exercising conscious dogs. J Pharmacol Exp Ther. 1995;275:659–66.PubMed
16.
Zurück zum Zitat Baumgart D, Haude M, Gorge G, et al. Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries. Circulation. 1999;99:2090–7.PubMed Baumgart D, Haude M, Gorge G, et al. Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries. Circulation. 1999;99:2090–7.PubMed
17.
Zurück zum Zitat Heusch G, Baumgart D, Camici P, et al. Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation. 2000;101:689–94.PubMed Heusch G, Baumgart D, Camici P, et al. Alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans. Circulation. 2000;101:689–94.PubMed
18.
Zurück zum Zitat Ceconi C, Comini L, Suffredini S, et al. Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling. Am J Physiol Heart Circ Physiol. 2011;300:H366–73.PubMedCrossRef Ceconi C, Comini L, Suffredini S, et al. Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling. Am J Physiol Heart Circ Physiol. 2011;300:H366–73.PubMedCrossRef
19.
Zurück zum Zitat Manz M, Reuter M, Lauck G, Omran H, Jung W. A single intravenous dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction. Cardiology. 2003;100:149–55.PubMedCrossRef Manz M, Reuter M, Lauck G, Omran H, Jung W. A single intravenous dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction. Cardiology. 2003;100:149–55.PubMedCrossRef
20.
Zurück zum Zitat Mulder P, Barbier S, Chagraoui A, et al. Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation. 2004;109:1674–9.PubMedCrossRef Mulder P, Barbier S, Chagraoui A, et al. Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure. Circulation. 2004;109:1674–9.PubMedCrossRef
21.
Zurück zum Zitat Ceconi C, Freedman SB, Tardif JC, et al. Effect of heart rate redution by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol. 2011;146:408–14.PubMedCrossRef Ceconi C, Freedman SB, Tardif JC, et al. Effect of heart rate redution by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL. Int J Cardiol. 2011;146:408–14.PubMedCrossRef
Metadaten
Titel
Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina
verfasst von
E. Amosova
E. Andrejev
I. Zaderey
U. Rudenko
C. Ceconi
R. Ferrari
Publikationsdatum
01.12.2011
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 6/2011
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-011-6327-3

Weitere Artikel der Ausgabe 6/2011

Cardiovascular Drugs and Therapy 6/2011 Zur Ausgabe

Screening-Mammografie offenbart erhöhtes Herz-Kreislauf-Risiko

26.04.2024 Mammografie Nachrichten

Routinemäßige Mammografien helfen, Brustkrebs frühzeitig zu erkennen. Anhand der Röntgenuntersuchung lassen sich aber auch kardiovaskuläre Risikopatientinnen identifizieren. Als zuverlässiger Anhaltspunkt gilt die Verkalkung der Brustarterien.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Adipositas-Medikament auch gegen Schlafapnoe wirksam

24.04.2024 Adipositas Nachrichten

Der als Antidiabetikum sowie zum Gewichtsmanagement zugelassene Wirkstoff Tirzepatid hat in Studien bei adipösen Patienten auch schlafbezogene Atmungsstörungen deutlich reduziert, informiert der Hersteller in einer Vorab-Meldung zum Studienausgang.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.